1. Field of the Invention
This invention relates to a novel protein for eliciting protective immune responses in animals against Cryptosporidium parvum, and recombinant DNA sequences which encode the protein.
2. Description of the Prior Art
The protozoan Cryptosporidium parvum, is spread by an oral-fecal route, infecting the intestinal epithelium and, to a lesser extent, the extraintestinal epithelia of a wide rare of mammalian species, causing severe diarrhea that can be life threatening. The young and immunosuppressed are at particularly high risk. Numerous reports of cryptosporidiosis in children attending day-care have been reported [Fayer and Ungar, Microbiol. Rev., 50(4) :458-483, (1986)]. Although in most individuals the disease is self-limiting and protective immunity develops after a primary infection, cryptosporidiosis is a major cause of death in immunodeficient hosts such as persons afflicted with AIDS. As in humans, the young of animals are most susceptible to infection. Cryptosporidiosis is also a major disease of dairy and beef calves in the United States. At present, no prophylactic therapy is available to prevent this parasitic disease in humans or animals [Fayer and Ungar, ibid, and Dubey et al., Cryptosporidiosis in Man and Animals, CRC Press, Boca Raton, Fla. (1990)].
Several researchers have shown, however, that in calves, mice and humans, administration of hyperimmune bovine colostrum (HBC), prepared by immunizing cows with extracts of C. parvum oocysts, can effectively confer passive immunity against cryptosporidiosis [Fayer et al., J. Parasitol. 75(1):151-153 (1989); Fayer et al., J. Parasitol. 75(3):393-397 (1989); Fayer et al., Infect. Immun. 58(9):2962-2965 (1990); Nord et al., AIDS 4:581-584 (1990); Tzipori et al., Br. J. Med. 293:1276-1277 (1986); Tzipori et al., Lancet 2:244-245 (1987); and Ungar et al., Gastroenterology 98:486-489 (1990)]. Also, monoclonal antibodies and immune serum specific for C. parvum sporozoites can neutralize the parasite and either prevent or lessen the severity of infection in animals [Bjorneby et al., J. Immunol. 145(1):298-304 (1990); Bjorneby et al., Infect. Immnun. 59(3):1172-1176 (1991); Perryman et., Infect. Immun. 58(1):257-259 (1990); Riggs and Perryman, Infect. Immun. 55 (9):2081-2087 (1987); and Tilley et al., Infect. Immun. 59 (3):1002-1007 (1991)]. Although protection against C. parvum may be achieved by this type of immunotherapy, the development of resistance to cryptosporidiosis is dependent upon T lymphocytes and secreted lymphokines, in particular, gamma-interferon [Gardner, Am. J. Trop. Med. Hyg. 44(1):49-62 (1991); Mead et al., J. Infect. Dis. 163:1297-1304 (1991); McDonald et al., Infect. Immun. 60 (8):3325-3331 (1992); and Ungar et al., J. Immunol. 147 (3):1014-1022 (1991)]. The humoral response leading to production of protective antibodies specific for C. parvum may be dependent upon T cell signaling, but in persons with severe immunodeficiency T cell-mediated immunity is dysfunctional. Passive administration of hyperimmune serum or colostrum that is inhibitory for cryptosporidial parasites may be the only viable alternative for preventing or treating infection in such individuals.